The main theme of this proposal is to examine the mechanisms that contribute to plasticity of behavior in mammalian and invertebrate nervous systems. We will use a combination of behavioral, electrophysiological, biochemical, morphological, and molecular genetic techniques to study problems that are related to the four main types of plasticity: learning, motivation, recovery from damage, and development. Individual research projects have been designed to promote interdisciplinary collaboration between ten individual laboratories. To simplify the cell and molecular analysis of plasticity, three principal experimental systems will be employed: 1. semi-intact or reduced systems in which neuronal activity can be recorded while the organism exhibits behavioral responses; 2. isolated intact ganglia, and 3. cell culture and brain slice systems in which experimental control can be greatly increased. We will use semi-intact and reduced preparations of vertebrates as well as invertebrates to investigate two types of problems: a) plasticity of motor behavior, using a restrained cat engaged in a multijoint movement task; and b) alterations of motivational state, using a preparation of the marine mollusc Aplysia, that exhibits various types of plasticity and switching of motivational states involving feeding. Isolated ganglia of Aplysia will also be employed. We will use cell culture to study synaptic plasticity and axonal growth of both vertebrate (PC12 cells, and spinal cord neurons) and invertebrate (Aplysia) neurons. Finally, brain slices will be used to study long-term potentiation, a model of vertebrate learning. A comparison of the mechanisms of different forms of plasticity in vertebrate and invertebrate neural systems should provide insights into general mechanisms that contribute to plasticity of behavior.